It's the question of why things are. It's just at its basic level, it's fascinating. And it's so satisfying if you get even the tiniest bit of something you think that's interesting in that. You hear a cell, like you're recording from cells in the brain. That listening to a cell, it's mind boggling. It's one of those things that does not get old. I'm John Fox, director of the Del Monte Institute for Neuroscience at the University of Rochester.
And I'm delighted to welcome you to another episode of Neuroscience Perspectives. Today, I'm absolutely thrilled to be joined by a very good friend of mine, Dr. Christopher Moore, who is the associate director of the Kearney Institute of Brain Science and professor of neuroscience and brain sciences at Brown University.
His research contributed to understanding how the brain processes information, has advanced our understanding of how brain dynamics relates perception, and provided us with new insights into important brain mechanisms related to sleep and sensory processing. Chris, I'm absolutely delighted to have you here today. It's really exciting to be here. It's fun to talk with you. And I think we're going to have a wide ranging conversation. But I want to dive in on something.
Most people who sit in the seat that you're sitting in, neuroscientists, neuroscience perspectives, studying neurons. And they study neurons and their dynamics. And you take a more expansive view. And I think you call it embodied neuroscience. Tell us why that? Why do we need to be thinking about a more expansive view?
Sure. Sure. So neuroscience is, of course, the name for studying the biology that underlies our behavior in that wonderfully, beautifully narcissistic quest to understand ourselves and think it might somehow turn into this, that we could somehow understand the cells that live behind it. And the problem we have with neuroscience, or maybe I should say neuroscience, we have a problem, is neuroscience is named after a cell type, which is a very famous cell type, which is neurons.
And neurons are wonderful. They're the crown jewel of how we see, how we act, how we perceive, how we have conversations. Amazing networks for remembering. However, there's really good evidence now, and there has been for a long time, that the biology that happens in us that creates behavior is so much more than neurons. And that's true at a lot of levels, but it's profoundly true at the level of wonderful cells like astrocytes, named after stars.
We're doing work that show that the blood vessels in the brain seem to be computing, that they're not just pizza delivery, but that actually their very local dynamics might do things like hold memories and help us to perceive. So most neuroscientists, self-defined neuroscientists, that's the name they give to themselves, don't have a problem with that idea. But when you name a field after a single cell type, it's going to bias the work of the field towards that cell type.
And we might miss out on understanding behavior and what causes it if we don't find a way to shake that up. So you're saying more, you know, I think there's a good appreciation now that in between our two ears, there's this mass of cells, and that it's not just neurons. We know there are support cells, glia, astrocytes, cells that move around. They don't just stay in the one place and all the rest of it. But you're going further.
You're saying that the blood supply, that the cells delivering blood to the brain are actually playing a role in cognition? Would you go that far? 100%. Absolutely. And I could be 100% wrong. But I'm 100% sure that we cannot rule it out. And that, John, actually we met when we were both much younger. And the reason we met was we were both fascinated by this new method of fMRI.
And the central idea of fMRI is you can map where meaningful activity is going on in the brain with regards to our behavior and our cognition by picking up the accumulation of vasodilation in the brain, meaning local areas where blood flows in the brain. And it's a beautiful method for that and really exciting way of looking inside the human brain without having to open up the skull or something like that. It's incredibly useful.
And it's incredibly useful precisely because local blood dynamics so nicely predict in a very subtle, often very measured way how the brain is doing its business with regards to behavior, with regards to activity. But let me lean into that. So I think in our naive way when you and I met 100 years ago, we won't get into it. We're old vampires. It's actually in the Habsburg Republic. So at that time, and I think many people would believe this today, so you have a vascular system, your blood flow.
And the job of that is to deliver nutrients and oxygen to tissue that's active. So neurons are very active. We're burning all kinds of energy to do the computations we're doing. But that ultimately, it was just the plumbing. And we were getting this proxy measure. And you're saying, no, that's not enough here. It is a wonderful rhythm in our field. So in the history of ideas, I think this probably happens in every field where they go through periods of domination of one idea.
And people kind of forget about the findings of the previous 20 years. And if you rediscover those, you can get a nature paper or a very fancy publication and get tenure. And every 20, 25, 30 years or so, there is a major paper that comes out and rediscovers the fact that fast dilations in the brain, the things that led us to fMRI that mark this, are not related to local need for glucose or oxygen. Your brain is a hog, not yours personally. That actually wasn't meant to. My brain's a hog, too.
It uses a huge amount of energy. Something like 20% of the body's energy goes into something that is only 2% of its mass. Just two pounds of tissue. Two pounds of tissue. It is a huge energetic sink. It has lots of energy flowing to it all the time. It has a huge reservoir. And there is no reason to believe that the really fast fluctuations that are tracked by these dynamics, that that's a feeding event.
In fact, every time people have looked, every time there's a new set of methods, they find, actually, it's not well, it doesn't match up. Now, even if it did match up, the body is opportunistic. And even if that local dilation, the local change in blood flow, did matter to supply local brain areas, it doesn't mean it can't do two things. It could be acting as a local way of conveying information of you and I both study attention.
And one of the great examples of attention is the cocktail party effect, where number one, you can block out the noise, and you and I have done this, and have a great conversation with somebody. It's just a wonderful. And then someone says, John, over there. And your attention, without even moving your eyes, immediately, they can feel it dragged away. Blood flow is amazing at tracking that. That kind of change in your brain doesn't seem to need any additional context to it.
It may actually be not only blood flow. It's not as if neurons aren't involved. It's just that we're not getting the whole picture unless we include these other cell types. I mean, it's completely fascinating and provocative. It's very provocative. You're definitely saying things that a lot of folks in the field would be mystified. That's a kind. Right. That's a kind word, putting it. So let's go to the timing component of this, which is super important.
Because again, maybe in our naivety, we would say, OK, when we're looking at the blood flow, we're looking at the brain's plumbing. And that really is fluid flow through vessels, ever smaller vessels as you get to the core of the stuff that matters where the neurons are living. And that happens on a slow time scale. It has to, right? Because it's like water flowing in the stream. Whereas our neurons and the networks are talking to each other in milliseconds, thousands of milliseconds.
This is why we can do what we're doing now with such rapidity. Yeah. So now, so we talked about that coupling, the temporal coupling there. It's a great question. It's a really, really deeply appropriate question, I think. Which is, we do have as much as the brain's a mystery, the world gives us clues as to the timing on which it has to operate to do certain things. So there are a variety of thoughts to bring to that. And it's as rich as the topic of behavior itself.
So right now, we're having a conversation. And humans love to talk. I mean, here we are. Particularly these two humans. These two humans are hard to shut up in a very, very good way, right? So humans love to talk. And I talk for a little while. And that's like a unit of me doing stuff. And then you will talk for a little while. It's a very relevant time scale of behavior. Incredibly relevant. Maybe it's the basis of human interaction. That happens on tens of seconds. And we're doing it now.
So one answer to the question of, can non-neural systems play a deep role in real-time behavior, is that real time has many meanings. That we live on a wake-sleep cycle, which is super important for behavior. We live on an hourly cycle. We live on a couple hours between my cups of coffee cycle. We live on, there's an old idea that alpha oscillations recycle every 22 minutes. Maybe it's a magical idea. But there's even teaching theory that goes with that.
And then there's a conversational time scale. So if you bought the thesis that maybe the vast culture was a tick too slow in some way. But let's revisit that in a second. You could still say that for a huge range of what it is to be us, the way in which we have ideas emerge, like when I'm talking and then you think of something that's like, oh, that's why Chris is wrong. But it takes a while to percolate as a thought. On that time scale, it's absolutely fine. Those time scales are fine. Exactly.
The other. Biological motion would be another good example. Like the speed of humans or animals is really on the second scale. And something you've studied really nicely and is one of the foundations, I think, of how most people think about cognition in the brain is perception is as much prediction as it is reception. It's a combination of those two words even. And prediction works on those time scales. So that's one answer.
Another answer is that you're totally right about the notion of ambient fluid. And I think that the fluid that's in us is a great reporter of all of the states, like how hungry are we? How thirsty are we? How much do we care to have social interaction versus be a bit introverted and reset our batteries? Like all those deep cues that we have. So it's like a superhighway of that kind of information. And admittedly, that might update on, say, minutes time scale or tens of seconds.
Something is released that changes what we need. But that's the kind of information that our brains evolved to deal with. In the wild, if you make a bad judgment about whether or not you should be meeting a need, you will be lunch for the hawk flying above you very quickly. But the other answer, and not to go on and on, but just to mention it, is the vasculature in work that we're doing now can have amazingly quick responses on the time scale of 100 milliseconds in its dynamics in a couple ways.
One is we're imaging the calcium activity in blood vessels, following on really nice work that's emerging in the field. And those events look like action potentials. They're amazing. They last. The fundamental sort of unit of information transfer between neurons. Absolutely.
When we think of networks like this and you see the vibrating brain and glowing, on the same time scale, more or less, as the rate of action potentials, you can have these very brief moments of electrical activity, calcium activity, in vessels. You might then say, OK, but actually in the wiring diagram behind us, a lot of people think of it as a big circuit diagram, a voltage map. You might say, well, but vessels, nobody has ever looked at the voltage of vessels in a behaving brain.
So it is an unseen universe of possibility that may just be happening there. And given how dense that network is, we don't even know to rule it out, because we've never had the methods to even see it. And so hopefully those methods are coming soon. You know, I remember the first time you described this hemoneural theory was on the side of the road near Washington Square Park. We were both visiting NYU. I don't remember why. I remember vividly as well. And you were very excited about it.
But it's a while back. Tell me about traction. Is it catching hold? Do you find other people? Yeah, I have to say, as a scientist, you have the papers you write that a wonderful postdoc of mine, Jessica Cardin, who's now very just a former guest with us here at Neuroscience. A former guest with you on this show, and who's now running a wonderful lab making amazing discoveries.
She and I published a paper in 2009, which easily is a paper of mine that's gotten the most attention, where we showed we could create brain oscillations like those that people think might relate to consciousness. And as Jess put it to me then, we did a great job of kicking down an open door. I said, final nail in the coffin. She's like, that's too morbid.
In other words, it's a famous paper in part because it takes things people thought they knew, but we were lucky to have elegant methods that kind of nailed it. And it was in a way that made people understand maybe how these oscillations could work. Those are exciting papers and wonderful contributions. And then as you and I both know, you have those papers you write because you're like, this is going to be true.
And admittedly, I might not be able to test it in my lifetime, but I got to put this down. It's almost like it really is honestly the stuff we're supposed to do. It's a big part of what we're supposed to do. There's two important questions that I wanted to ask you. So as long as I've known you, you are one of those people who's trying to think outside the box and just really push the boundaries. And I know right now you're on a sabbatical, which folks may not even know what that is.
So we'll explain that. You can do it. But I was struck by some of the stuff that you said earlier today around just being thoughtful and taking some time to think. And is this sabbatical a key thing for you right now? Is it an important moment in your career? Yeah, absolutely.
So sabbatical is a wonderful thing in the life of being an educator, which is every seven years or so, you're allowed to take some time where you're allowed to try and think about problems and get in touch with ideas that maybe you didn't have time to go deep because you were teaching a lot of classes and writing a lot of grants and serving as a really ineffective middle manager of academia. All these things that we get to be part of. Right, that we have no training for.
That we have no training for. And we are blessed to get to doing podcasts. So it gives you the right to be allowed to be a nerd and really nerd out and be weird. And that brings me to the other side of that question, which is, of course, the way our system is set up and the funding models and that keep us in a safe space a bit, right? The old days where you could take time to really ferment and mature an idea or dive deep or try some wacky stuff.
That's hard to do in this modern environment, right? I think it is literally our job to keep trying. And I think you're absolutely right. That there's a concept in people who think about science as an overall thing that is done in the world of the paradigm. And the idea of a paradigm, I always like to think of it as like a haystack. It's a tendency of the hay to be in the stack of belief, right? And it's our job to try and find out true things, not to find out things that are for the sake of it.
But part of our job is to see if the haystack has no close. And one of the most mixed metaphors in the history of your podcast, if not the history of mankind. It's our job to say, wait a minute. Wait a minute, what are we missing? That is part of it. It's not the sole part of our job. We also have to do things. Doing something that will matter for human health is maybe the paramount part of our job, right? And that will have a lot of different things you need to do.
And some, that said, doing things that have what we refer to as discovery value, which is the degree to which you might change the way we think about the brain, I think has a role in the portfolio, the investment of time portfolio that we all have. So do you find yourself now on sabbatical, that you've parked things at the lab. I presume you've got some management there that's, or do you find yourself drawn back? I have a great lab. Do you find yourself in a different mode of thinking?
Is it different? Are you approaching life for this period of time in a different way? It's just a great question. So I mean, I'm actually interested, because of course, you've made tremendous creative contributions to our field. And it takes work, right? It does, yeah, absolutely. It takes work, and it takes, and again, thinking back to absolutely fabulous conversations we've had at many moments, including in Cambridge, Mass, where I remember meeting, it takes practice to try to be weird.
I mean that in the fullest sense. You need to find the National Geographic documentaries, where you see the lion cubs playing, and the voiceover says, and now they're practicing hunting on the brothers and sisters. It's the sisters, right, though, because the lioness is doing all the hunting.
OK, you've got to always have an attitude to that lion cub of finding your good friends that you trust, that won't be upset that you tried an idea on them, but won't fail to be critical in that useful way also. It's work, but it's fun. You can have fun trying out a crazy idea on. You have to practice that to be able to do it. It's a muscle, too. So that leads me to a thought, too, as well, because I worry about this a lot. I think you and I arrived into science at a really great time.
We were both extraordinarily lucky to be at Mass General at the advent of functional magnetic resonance imaging. And I always say this, a lot of it's luck. But I worry about youngsters today. We had a lot of latitude that I'm not sure they do now. There's a programmed component to the way youngsters go through grad school. Are you worried about that? What do you say to your own graduate students? I'm incredibly worried. Neil Young has a great quote that there's a lot to learn for wasting time.
And actually, Rick Rubin, who wrote a fabulous book on discovery and creativity, The Creative Act, an absolutely wonderful book. I can't recommend it. Get it on audio, because he is, of course, a god of recording. And he reads the book to you, which is just. And there's something about having time to make mistakes. So would you recommend that to a graduate student? Go to this book. I have given it to any number of people. It's almost like, here, take this. You know that feeling. Yeah, of course.
But it's really tricky, because some people also want to do things that are different. I think being creative has to be a part of what you do. That doesn't mean it has to be your North Star all the time. Everyone's going to have a different. It takes a team in science. Controlled creativity. Because I sometimes have a youngster come to me, and they've got a fantastic idea. And I say, that's great. There's literally no way to measure that, given the tools we have available.
You're going to have to constrain this. Yes. You know, there are fabulous ideas and ideas you can test. What you'd love to do, and we so rarely achieve. But the dawn of fMRI was a time to do it, where that intersection was well-posed. And that's why sometimes people are accused of chasing methods. And they're always trying to add some fancy new method. Hopefully, you're guided by knowing, oh, if I can just get this to work, there's an idea. I think everyone would have wanted the answer to.
But if we can just get this to work, it's just so frustrating. I appreciate that. Let's go back a little bit to science. I saw some images that you were showing of pancreatic cells, ensembles of cells, electrically coupled, communicating with each other. Going back to this embodied mind, embodied body, this holistic thought about the whole organism, is that a form of neural activity? How are you thinking about that? The word embodiment has a really cool history.
It came on the scene in neuroscience in the early 1990s, when another fabulous book, The Embodied Mind, by Varela Thompson and Roche, a philosopher, a psychologist, and a biologist with very strong psychology and philosophical skills, Varela, wrote. And the idea of the embodied mind was we're not going to get the answer of behavior right, unless we think of all the ways in which our sense of our own self and our sense of behavior is situated. It's situated in the world.
We're not going to understand who we are, except that we're defined a lot by our good conversations, which is why it's great to hang out with you and why we've been hanging out for decades. You know what it put me in mind of today is, here at Rochester, in medicine, this is the home of the biopsychosocial model of medicine. Yes. And it was a way to stop seeing human beings.
So I'm not talking about neuroscience anymore, really, but stop seeing human beings as the disease that they walk through the door with them, but to see them as a holistic person that had a biology disease, but a psychology and a social setting. And that those three combined really defined the phenotype, the clinical presentation. And it was a game changer in medicine. And the biopsychosocial model has gone everywhere.
But I was thinking about that today with you when you were talking about the brain as not this thing that's just sitting in there protected by the skull, but that it's part of a much more interactive system. I agree. And that is a fabulous point of reference for this. We really will not understand someone's illness or even how you're going to be able to approach it in a way that could reach them. I mean, the body is going to do the best work. So you have to get them behind it if you're going to.
Your point's just fabulous. So the word embodied is often used for how we're situated that way. We're situated in the world. There's another notion of embodiment which is completely continuous with it, which is we like kings and queens. We really like to see things as top down. And we have this notion that we have a mind. And our mind lets us do stuff. I don't think it's wrong. It's a real feeling. I don't know. You feel that way, right? Yeah, sure.
You don't feel like a distributed set of atoms that happen to be accidentally created by a violation of entropy. I like this shirt. And I like it. And I like to play Magic the Gathering with my son. He beats me, but I still like it. That feeling makes us feel as if there's like a leader in our head that's in charge of our thoughts. It's the most intuitive way we can think about things. And so it absolutely is. We think, and therefore we are. That view is not wrong. That's our phenomenology.
That's our OK. I think partly because we love that view. And we love it for a good reason. It's our experience. There's every good reason to love it. Partly because we love that view. We love the idea that there's a super fancy kind of cell that humans must have more of. And it's that magic cell that does this magic computation. And it's like the battery in a Tesla, or it's like the secret sauce in our favorite super successful restaurant's meal. That's the thing that makes it different.
That's not probably wrong at some level. But we really like the hierarchical idea. And I think that when we think of embodiment as you absolutely cannot make an airtight argument that the immune system isn't controlling your behavior as much as neurons are, it's a wonderful debate point to try and chase that down. Immune cells learn. Immune cells respond to the environment to work for your preservation to lead to adaptive behaviors. And through really complex memory.
I mean, the immune system's amazing. You get chicken pox when you're 10. And you might, well, of course, we might get other diseases later. But for now, right? Yeah. And somehow it remembers it without getting the function. And you don't just remember one thing. You remember tens of thousands of diseases. Right, yeah. OK? Things that adaptively learn and change your behavior and have amazing resolution and information bit depth. That sounds like cognition. Fair enough.
It's almost entirely continuous. They just don't have the levers to your motor system the way your neurons do. Well, OK. But here's a way to think about it. Let's do this. OK, let's do this together. We reach down to get our glass of water. Because we're forming a very fancy neuroscience perspective mug. So we have our neuroscience perspective mug. We reach down.
Now, most of the time when I think about that, most of my colleagues who say they work on motor control or the act of doing that actually record from neurons in the brain. Now, did my muscles do the computation? Let's imagine we're going to say they didn't. That's OK. And we'll say the neurons did do it. So we think the interesting thing that makes us us was the motor neurons. And this was just implementational after that. Why can't we think of the neurons as just, that's a muscle.
It's a relay from our immune system to moving stuff. Yeah, you need the neurons. They're nice. They do a transformation of the actual computation, which is occurring in the pancreas or the immune system or the vasculature. And there's a downstream necessary thing, which is it uses the neurons. It's nice to have them around. That isn't actually my view. I think it's a much more cooperative thing. But you see by analogy, we disregard all kinds of things are essential to a process.
Because we view them as derivative or simply playing out the commands of another part of the process. Why can't the immune system be commanding the neurons in our brain the same way? I guess the point is the question actually hasn't been asked, technically. And the more we study it, the more we find.
The more we find that our guts, our microbiome in our gut, does an amazing job of regulating our reward system, which in turn does an amazing job of regulating whether we stay up too late and play that extra game or make a choice about dessert that maybe we regret later. Or maybe we shouldn't regret it. And maybe when we have dinner tonight. Absolutely. Yeah. Let me ask you a little bit. Let's go back to the youngster that was Chris Moore, short pants, heading off to school.
Was it all was going to be science? I have it on good authority that at one point you started writing in ABCs of the brain or something when you were a kid. Wow, this is dangerous. Background intel. We have very good researchers here. Let me ask you a question. I want to ask you a question too, because again, I think we have such a set of parallelisms in lots of ways. Do you think of yourself as a scientist? That's a good question. Boy. In part. A little. Yeah. I do. I guess the answer is yes.
I think I do too. I, of course, think of you as one. And I think of myself as one. I certainly think of you as one. I'm certainly happy to have that as our job name, like fire person or police person, or we could even be less non-gendered about that. I don't know though. Don't you feel like you're a person trying to figure out stuff in a way that will actually help people the most? Yeah, for sure. Science is an amazing vehicle, and you're trained in it.
So I guess I'm not trying to be overly dramatic about this. No, that's OK. No, but these things keep us both up at night. So it was that. It's the driving force. It may not have been that I want to be a scientist, but I want to answer questions that matter to people. And that came early. Yes, and absolutely. Let me ask you another question too. This is not how it's supposed to work, but it's OK. No, no, no. But I'm partly doing it to stall so I can make sure I've got my answer well posed before.
But when did you become an addict of discovering stuff? Oh, it's good. Yeah. Well, see, I had a very different trajectory into science, so I started very late. Actually, my undergraduate was in English and history and literature. And I came over here to the States. I started science after I came to the States, and I had a previous career for a little while as a track and field person. So it came late. But funnily enough, I think the way of thinking was almost there. That was there.
And I had one of those things where I loved science courses in school, but I had all the teachers telling me, well, you really should go into the humanities. You're better. You're a good writer, and so on. So I ended up sort of, it was a circuitous route back to it for me. But I'm with you on the mode of thought. I was always super inquisitive, and I really did not like people giving me pat answers to things where they couldn't explain why.
So I was that kid who kept saying why way past the due date. That was fabulous, actually. So to the question of are we scientists, of course. And I'm super comfortable with that definition, certainly professionally, 100%. But I do think, I don't know. I feel like a person who's blessed to work in a field where my addiction can be satisfied. Every day, it's so exciting when you learn something new.
And to think that you can turn that into operational knowledge that might somehow help the world go forward. You studied philosophy. There's this idea of positivism that's learning more and knowing more about the world will help the world. Widely debated with Oppenheimer, the movie having recently come out that we learn more and that we learned how to make nuclear bombs. I will admit it, I'm a positivist.
I actually think that openness and communication and the search for more knowledge is the way to get past all the crappy things we do as humans. I totally agree. I could not agree more. And given that belief, then it's easy for me to feel like it's deep to want to learn stuff if you buy into that view. Because it is a path to helping people. It's really fantastic. If it hadn't been science, if the big job fair in the sky came out and said, I'm sorry, Chris, it's out. You can't be.
Would you have done something else? Is there something else that's sort of burning there? That's a great question. I want to be really clear about something, too. I honestly think I became a scientist just out of curiosity. I was so much a fan of discovery, of people discovering things that could change the way we think about how they work. And science was one really exciting. I was also a philosophy major. I was very gratified. We mentioned Rick Rubin earlier.
I was gratified to learn that until he switched to his something like television media major, he was a philosophy major. As was, I just learned Phil Jackson, the bull's coach. And I think I probably was for the same reason you were interested in the topic, the more broader thinking topics of humanities. It's the question of why things are. It just at its basic level is fascinating. And it's so satisfying if you get even the tiniest bit of something you think that's interesting in that.
You hear a cell, like you're recording from cells in the brain. Yeah. Listening to a cell is mind boggling. It's one of those things that does not get old. Well, Chris Moore, you are an original thinker. I imagine that the students at Brown get a great kick out of you and your lectures and all the students that are associated with you. It's been an absolute pleasure having you here. It's been a pleasure knowing you over the years. Absolutely my pleasure. Great conversations ahead.
Yeah, absolutely. Thanks a lot, John. Thank you. This is a lot of fun. Are you excited we're starting to start steel industry and,이었 Gerald? Yep. Good to hear you. Very. Um, so very excited to have you here guys is it's a lower than it seems it has been since
